Hu14.18-IL2 with GM-CSF and Isotretinoin in Relapsed NB
See article by Shusterman et al., p. 6044
A standard minimal residual disease therapy for children with high-risk neuroblastoma is the combination of anti-GD2 monoclonal antibody with GM-CSF, IL2 and isotretinoin. Half of children with this disease, however, will succumb to recurrent disease. In this phase II clinical trial, Shusterman and colleagues investigated the utility of a humanized anti-GD2 antibody conjugated to IL2 (Hu14.18-IL2) in combination with GM-CSF and isotretinoin. This altered regimen was, generally, well tolerated. Furthermore, 5 of 31 patients demonstrated an objective response to this combination, with responses only observed in patients with non-bulky disease. These results support continued assessment of Hu14.18-IL2 in neuroblastoma.
PD-L1 and Clinical Outcomes to Cabozantinib in Renal Cancer
See article by Flaifel et al., p. 6080
Despite recent advances in the treatment of metastatic renal cell carcinoma, effective biomarkers remain unidentified. Flaifel and colleagues assessed the association of PD-L1 expression levels with response to targeted therapies using baseline tissue biopsies from the METEOR and CABOSUN trials. Patients whose tumor cells express PD-L1 had poor prognosis, regardless of treatment. Furthermore, cabozantinib treatment was superior to treatment with everolimus or sunitinib, regardless of PD-L1 expression. These results strongly favor the incorporation of cabozantinib into first-line therapeutic strategies for metastatic renal cell carcinoma, particularly those negative for PD-L1.
Circulating Tumor Cell Clusters within SWOG S0500 Study
See article by Paoletti et al., p. 6089
Recent work has proposed the importance of clusters of circulating tumor cells (CTCs) in metastasis. To address this potential marker in breast cancer, Paoletti and colleagues analyzed CTC data from the SWOG S0500 trial. Patients who had CTC doublets and/or clusters at baseline had poorer overall survival than patients without CTC doublets/clusters. However, doublets/clusters were correlated with higher levels of total baseline CTCs, indicating that the poor prognosis seen in these patients may instead be a function of higher total CTC levels. To this end, there was no significant difference in overall survival among patients with high levels of CTCs when stratified by the presence or absence of doublets/clusters. These data challenge the notion that CTC clusters are prognostic in cancer, indicating that more stringent analysis of this potential marker is needed across cancer types.
Circulating Tumor DNA Profiling in SCLC
See article by Devarakonda et al., p. 6119
Patients with relapsed small-cell lung cancer (SCLC) rarely undergo biopsy, and when they do, the tissue is often insufficient for molecular analysis. In this study, Devarakonda and colleagues assessed ctDNA profiles of SCLC patients using the commercially available Guardant360 platform. Using this platform, mutations were identified in actionable targets, including DNA repair genes, members of the MAPK and PI3K pathways, and the androgen receptor. Furthermore, the test turnaround time was sufficiently short to impact treatment decisions (median 14 days). These results suggest that this NGS platform for ctDNA has the potential to guide clinical decisions for SCLC patients.